Investigating Respiratory Disease Outbreaks:

1
Investigating Respiratory Disease Outbreaks
An integrated approach to investigations,
specimen collection, and pathogen identification

Lauri A. Hicks, DO CDCs Respiratory Outbreak
Working Group March 3, 2009
2
Continuing Education Disclaimer

• In compliance with continuing education
  requirements, all presenters must disclose any
  financial or other relationships with the
  manufacturers of commercial products, suppliers
  of commercial services, or commercial supporters
  as well as any use of unlabeled product(s) or
  product(s) under investigational use. CDC, our
  planners, and the presenters for this seminar do
  not have financial or other relationships with
  the manufacturers of commercial products,
  suppliers of commercial services, or commercial
  supporters. This presentation does not involve
  the unlabeled use of a product or product under
  investigational use.
• There is no commercial support.

3
Accrediting Statements

• CME The Centers for Disease Control and
  Prevention is accredited by the Accreditation
  Council for Continuing Medical Education (ACCME)
  to provide continuing medical education for
  physicians. The Centers for Disease Control and
  Prevention designates this educational activity
  for a maximum of 1 AMA PRA Category 1 Credit.
  Physicians should only claim credit commensurate
  with the extent of their participation in the
  activity.
• CNE The Centers for Disease Control and
  Prevention is accredited as a provider of
  Continuing Nursing Education by the American
  Nurses Credentialing Center's Commission on
  Accreditation. This activity provides 1 contact
  hour.
• CEU The CDC has been approved as an Authorized
  Provider by the International Association for
  Continuing Education and Training (IACET), 8405
  Greensboro Drive, Suite 800, McLean, VA 22102.
  The CDC is authorized by IACET to offer 0.1 CEU's
  for this program.
• CECH The Centers for Disease Control and
  Prevention is a designated provider of continuing
  education contact hours (CECH) in health
  education by the National Commission for Health
  Education Credentialing, Inc. This program is a
  designated event for the CHES to receive 1
  Category I contact hour in health education, CDC
  provider number GA0082.

4
Objectives

• Describe the clinical and public
  health challenges associated with respiratory
  disease outbreaks
• Discuss CDCs approach to support outbreak
  investigations
• Introduce the Unexplained Respiratory Disease
  Outbreak website
• Describe new diagnostics that will be useful for
  investigating outbreaks

5
Continuing Education Credit/Contact Hours for
COCA Conference Calls

• Continuing Education guidelines require that the
  attendance of all who participate in COCA
  Conference Calls be properly documented. ALL
  Continuing Education credits/contact hours (CME,
  CNE, CEU and CECH) for COCA Conference Calls are
  issued online through the CDC Training
  Continuing Education Online system
  http//www2a.cdc.gov/TCEOnline/.  
• Those who participate in the COCA Conference
  Calls and who wish to receive continuing
  education and will complete the online evaluation
  by April2, 2009 will use the course code EC1265.
  Those who wish to receive continuing education
  and will complete the online evaluation between
  April 3, 2009 and March 3, 2010 will use course
  code WD1265. CE certificates can be printed
  immediately upon completion of your online
  evaluation. A cumulative transcript of all
  CDC/ATSDR CEs obtained through the CDC Training
  Continuing Education Online System will be
  maintained for each user.

6
Respiratory Outbreaks Challenges

• Differentiating outbreaks from sporadic disease
  can be difficult
• Baseline disease rates often unknown
• Seasonality cyclical increases in sporadic
  disease expected
• Wide range of pathogens can cause similar
  clinical syndromes
• Viral, bacterial, fungal
• Outbreaks may involve multiple etiologies
• Potential new pathogens

7
New Pathogens

• Old pathogens with new characteristics
• Adenovirus14
• XDRTB
• Newly described potential pathogens
• Human bocavirus
• Human coronaviruses NL63 and HKU1

8
Respiratory Outbreaks More challenges

• Adequate commercially-available diagnostics often
  lacking
• Limited state laboratory diagnostic capacity
• Epidemiology and laboratory response may not be
  integrated

9
Pertussis Puzzle

• Laboratory worker at hospital presented to clinic
• Symptoms classic for pertussis
• Tested positive with hospitals PCR assay
• Active screening implemented
• 1000 of 6289 healthcare workers tested, treated,
  and furloughed for suspected pertussis
• 2300 azithromycin packs distributed
• gt4500 doses Tdap given

MMWR 56(33) 837-842
10
The Pertussis Epidemic that Wasnt Pertussis

• 134 cases identified
• No cultures positive
• Confirmatory testing showed no evidence of a
  pertussis outbreak
• Outbreak of mild respiratory disease with no
  single etiology

Faith in Quick Test Leads to Epidemic That Wasn't

New York Times, January 22, 2007
MMWR 56(33) 837-842
11
Whooping Challenges

• Differential diagnosis large
• Diagnostic tests used to define outbreaks
  unreliable
• Outbreaks overwhelm local resources
• Result in delay in identifying the etiology,
  negative media attention, and further promotion
  of anti-vaccine mentality

12
Which Outbreaks Should be Investigated?

• Unusual outbreak characteristics
• Unknown etiology or clarification of causative
  agent(s) needed
• Severe disease
• Large or rapidly progressing
• Potential BT event
• Vulnerable population
• Potential intervention
• vaccine, environmental intervention, institution
  (infection control)
• Advance knowledge
• Epidemiologic e.g., disease or transmission
  characteristics
• Laboratory e.g., diagnostic test evaluation
• Infection/disease controle.g., vaccine or
  intervention effectiveness
• Demand--excessive public anxiety

13
Historical Challenges at CDC

• Lacked a unified approach to handle unexplained
  respiratory disease outbreaks
• Communication among CDC respiratory disease
  experts challenging
• Coordination of specimen collection and
  laboratory testing lacking
• May hinder recognition of the etiology for the
  outbreak delaying effective control measures
• Limited tools and resources for public health
  partners

Silos
14
Moving Towards a Solution

• CDC Respiratory Outbreak Working Group formed in
  2004
• Currently 43 members
• Multi-disciplinary group reaches across
  divisional and center boundaries
• Overall goal Optimize public health
  preparedness and response to respiratory disease
  outbreaks

15
(No Transcript)
16
CDCs Respiratory Outbreak Working Group

• Objective 1 Streamline and coordinate CDCs
  epidemiologic and laboratory response to requests
  for assistance

17
Working Group Consultations Since March 2007

• Consultations provided for 18 22 unexplained
  outbreaks
• Working group conference calls 16 20
• Laboratory support provided 14 18
• Epi-aid investigations 4
• Location for requests
• Domestic 12 15
• International 7 (including Australia, Panama,
  St. Croix, Kenya, Taiwan, and Nicaragua)
• Outbreak etiologies include Mycoplasma
  pneumoniae, Bordetella pertussis, adenovirus,
  respiratory syncytial virus, Mycobacterium
  tuberculosis, parainfluenza virus 3, and influenza

18
Objective 1 Streamline and Coordinate CDCs
Response
19
Unexplained Outbreak, St. Croix, U.S. Virgin
Islands--December, 2007

• December 2007 working group notified of an
  unexplained outbreak of cough illness among
  school children in St. Croix
• Conference call organized to provide emergent
  advice to health officials
• Epi-Aid field investigation launched
• Respiratory outbreak team assisted with field
  investigation

20
Unexplained Outbreak, St. Croix, U.S. Virgin
Islands--December, 2007

• Specimens collected by team
• Rapid, coordinated laboratory response
• Simultaneous testing for multiple pathogens
• Pertussis identified as primary etiology

21
Unexplained Outbreak, Prince of Wales Island,
Alaska--September, 2008

• 30 September AK notifies CDC (10 pts, 3
  hospitalized, 1 death)
• 1 Oct CDC WG conference call with AK
• 3 Oct CDC receives specimens for testing four
  specimens positive for adenovirus 14
• 12 October five-member AK DoH/CDC team arrives
  to assist with investigation

22
CDCs Respiratory Outbreak Working Group

• Objective 1 Streamline and coordinate CDCs
  epidemiologic and laboratory response to requests
  for assistance
• Objective 2 Develop a website to provide
  background, guidance and tools for investigation
  of outbreaks

23
Purpose of the Unexplained Respiratory Disease
Outbreak Website

• Build capacity to respond to and investigate
  respiratory disease outbreaks
• Provide tools that will lead to the timely
  identification of the etiology of an outbreak and
  facilitate disease control efforts
• Primary audience State and local health
  departments

24
http//emergency.cdc.gov/urdo/
25
What Defines an Outbreak?

• An outbreak or cluster of respiratory disease is
  illness in excess of what would expected for a
  given time and location

26
Develop a Case Definition
27
(No Transcript)
28
Data Collection Forms
29
Differential Diagnosis Clues

• Principle respiratory syndrome or associated
  syndromes
• Age and population characteristics
• Season and location
• Exposures

30
Generate a Differential Diagnosis
31
Guidance for Specimen Collection

• What specimens should we collect?
• How should we collect them?
• How should they be stored?

32
Tools for Specimen Collection
33
CDCs Respiratory Outbreak Working Group

• Objective 1 Streamline and coordinate CDCs
  epidemiologic and laboratory response to requests
  for assistance
• Objective 2 Develop a website to provide
  background, guidance and tools for investigation
  of outbreaks
• Objective 3 Increase laboratory capacity to test
  for multiple pathogens

34
Identifying Respiratory Pathogens
Develop diagnostic assay
Transfer technology, train, proficiency test
35
Real-Time PCR Assays in Development

• Currently available only at CDC, but many of the
  protocols will be made available on the APHL
  website
• New assays
• Detection and genotyping C. psittaci
• Bacterial and viral subtyping M. pneumoniae, L.
  pneumophila (16 serogroups), human coronaviruses,
  rhinoviruses, bocaviruses
• Macrolide resistance M. pneumoniae
• New specimens
• Serum, CSF for S. pneumoniae

36
Multiple Pathogen Assays (MPAs)

• Based upon lyophilization of real-time PCR
  reagents
• Allows convenient testing for several agents in a
  short period of time
• Can be stored for immediate use in emergencies
• Two approaches are under investigation 1)
  Taqman Low-density Array (TLDA) cards and 2) 8
  well strip tubes

37
TaqMan Low Density Array Card
38
Strip Tubes

• Will probably replace the TLDA cards in the
  future
• 8 well strip tubes contain real-time PCR reagents
  
• Configured in a way that increases flexibility
  and decreases cost
• Currently preparing prototype tubes for validation

39
Recent Advances in Diagnostics

• Offer the potential for detection of multiple
  pathogens from a single specimen
• MPAs could be extremely valuable for
  surveillance, use in outbreaks of unknown
  etiology, and early response to pandemic
  influenza
• CDC would like to work with states on validation
  of new lab tests in the setting of respiratory
  outbreaks

40
Current Efforts

• Develop multi-pathogen diagnostics
• Build virtual world training module with model
  outbreak scenario
• Increase awareness of availability of Website and
  Respiratory Outbreak Working Group

41
Unexplained Respiratory Disease Outbreaks

• Investigations require an integrated
  epidemiologic and laboratory approach
• CDCs Respiratory Outbreak Working Group is
  available to assist with outbreaks
• The Unexplained Respiratory Disease Outbreak
  website is a resource for investigating outbreaks

42
Resources

• When faced with a cluster of respiratory disease,
  ask Do we know what is causing this?
• If help needed, contact your State or Local
  Health Department and consider consulting the
  Respiratory Outbreak Working Group
• CDCs Emergency Operations Center
• (770-488-7100)
• Website http//emergency.cdc.gov/urdo/

43
CDCs Respiratory Outbreak Working Group

• Bacterial Respiratory
• Influenza
• Viral Respiratory
• Meningitis and Vaccine Preventable Diseases
• Pathology
• Vectorborne Diseases
• Mycotic Diseases
• Special Pathogens
• Specimen Management
• Emerging Infections
• Bacterial Zoonoses
• Prevention and Response

• Special thanks!
• Steering committee
• Chris Van Beneden
• Nicole Alexander
• Christine Dao
• Mary Wikswo
• Ashley LaMonte
• Eileen Schneider
• Janine Cory
• Stacey Thalken

44
Disclaimer

• The findings and conclusions in this
  presentation have not been formally disseminated
  by the Centers for Disease Control and Prevention
  and should not be construed to represent any
  agency determination or policy.